The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis
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BACKGROUND: The circulating levels of plasminogen activator inhibitor type 1 (PAI-1) are increased in individuals carrying the 4G allele at position -675 of the PAI-1 gene. In turn, overexpression of PAI-1 has been found to affect both atheroma and thrombosis. However, the association between PAI-1 levels and the incidence of myocardial infarction (MI) is complicated by the potentially confounding effects of well-known cardiovascular risk factors. The current study tried to investigate in parallel the association of PAI-1 activity with the PAI-1 4G/5G polymorphism, with MI, and some components of metabolic syndrome (MetS). METHODS: Using meta-analytical Mendelian randomization approaches, genotype-disease and genotype-phenotype associations were modeled simultaneously. RESULTS: According to an additive model of inheritance and the Mendelian randomization approach, the MI-related odd ratio for individuals carrying the 4G allele was 1.088 with 95% confidence interval (CI) 1.007, 1.175. Moreover, the 4G carriers had, on average, higher PAI-1 activity than 5G carriers by 1.136 units (95% CI 0.738, 1.533). The meta-regression analyses showed that the levels of triglycerides (p=0.005), cholesterol (p=0.037) and PAI-1 (p=0.021) in controls were associated with the MI risk conferred by the 4G carriers. CONCLUSIONS: The Mendelian randomization meta-analysis confirmed previous knowledge that the PAI-1 4G allele slightly increases the risk for MI. In addition, it supports the notion that PAI-1 activity and established cardiovascular determinants, such as cholesterol and triglyceride levels, could lie in the etiological pathway from PAI-1 4G allele to the occurrence of MI. Further research is warranted to elucidate these interactions.
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High levels of fibrinogen and plasminogen activator inhibitor-1 (PAI-1) are markers for ASCVD.
“High levels of fibrinogen and plasminogen activator inhibitor-1 (PAI-1) are markers for ASCVD. (Evidence level: E-1a)”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [303]
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- Authors
- Nikolopoulos, G. K., Bagos, P. G., Tsangaris, I., Tsiara, C. G., Kopterides, P., Vaiopoulos, A., Kapsimali, V., Bonovas, S., & Tsantes, A. E.
- Affiliations
- University of Thessaly (GR)
- Corresponding author
- Nikolopoulos, Georgios K.
- Bagos, Pantelis G.
- Tsangaris, Iraklis
- Tsiara, Chrissa G.
- Kopterides, Petros
- Kapsimali, Violetta
- Bonovas, Stefanos
- ORCID
- Venue
- Clinical Chemistry and Laboratory Medicine (CCLM)
- Publisher
- Walter de Gruyter GmbH
- Published
- 2014-01-01
- Volume
- 52
- Issue
- 7
- Pages
- 937-50
- ISSN
- 1434-6621 (ISSN-L)
- 1437-4331
- OpenAlex
- W1985578174
- Cited by
- 42
- References
- 112
- Citations by year
- 2026: 1 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 6 · 2019: 4 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Chemistry and Laboratory Medicine (CCLM) (publishedVersion)
- PubMed (publishedVersion)
- University of Thessaly Institutional Repository (University of Thessaly) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- plasminogen activator inhibitor-1, PAI-1 4G/5G polymorphism, myocardial infarction, genetic susceptibility, metabolic syndrome, triglycerides, cholesterol, cardiovascular risk factors, thrombosis, atherosclerotic plaque
- MeSH terms
- Alleles, Humans, Myocardial Infarction, Polymorphism, Genetic, Plasminogen Activator Inhibitor 1, Mendelian Randomization Analysis
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